Page 203 - Haematologica Atlas of Hematologic Cytology

CHAPTER 23 - Megaloblastic anemia
Chapter 23. MEGALOBLASTIC ANEMIAS
Macrocy c anemias are usually classi ed into megaloblas c or non-megaloblas c. Megaloblas c forms are indu- ced by de ciency or defec ve u liza on of cobalamin and/or folate resul ng in impaired DNA synthesis. The many causes of megaloblas c anemia are listed in Table 1 (Green and a a Mi ra ).
Defec ve DNA synthesis induces typical morphological abnormali es both in the bone marrow (BM) and periphe- ral blood (PB) cells. Thus, evalua on of blood and BM smears plays an essen al role in raising the suspicion of these diseases and in di eren a ng non-megaloblas c from megaloblas c anemias in pa ents with macrocy c anemia.
As detailed in the legends of the gures in this chapter, the most common morphological abnormali es observed in PB are the presence of a variable percentage of macro-ovalocytes in the context of various other abnormali es in the shape of red cells and hypersegmented granulocytes. In the BM, there is high cellularity with an excess of erythroid precursors that are larger than normal and characterized by nuclear-cytoplasmic matura on asynchrony. Impairment of DNA synthesis also a ects the other hematopoie c series, but the resul ng func onal and morpho- logical changes are less striking. In fact, anemia is an almost constant feature of these condi ons, while clinically relevant thrombocytopenia and leukopenia are observed only in the most advanced forms.
None of the numerous morphological altera ons of blood and BM cells are in themselves of diagnos c value, but rather it is their coexistence in the same pa ent that should suggest a megaloblas c anemia.
Table 1. auses of megaloblas c anemia.
obalamin de ciency Decreased intake
e a e e aria
Defec ve absorp on

Folate de ciency
er icio a emia a rec om ileal re ec o olli er lli o rome li loo rome i a e orm i e a o a crea c i cie c
Decreased intake
ri o al e cie c ie oa mil e c ie e or o mo er i ola e e cie c
Defec ve absorp on
eliac i ea e a ro ical r e
Increased demand

Drug induced
re a c
er ro ic emol c a emia olia e erma emo ial i
An bio cs, an metabolites Dihydrofolate reductase inhibitor Inhibitors of deoxynucleo de synthesis An convulsants
Oral contracep ves
Inborn errors of metabolism Cobalamin de ciency
Errors of cobalamin and folate metabolism
Reference
Green R, Da a Mitra A. Megaloblas c Anemias: Nutri onal and Other Causes. Med Clin North Am. 2017;101(2):297-317.
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